Systems, apparatuses, and methods for protecting electronic components from high power noise induced by high voltage pulses

ABSTRACT

Systems, devices, and methods for electroporation ablation therapy are disclosed, with a protection device for isolating electronic circuitry, devices, and/or other components from a set of electrodes during a cardiac ablation procedure. A system can include a first set of electrodes disposable near cardiac tissue of a heart and a second set of electrodes disposable in contact with patient anatomy. The system can further include a signal generator configured to generate a pulse waveform, where the signal generator coupled to the first set of electrodes and configured to repeatedly deliver the pulse waveform to the first set of electrodes. The system can further include a protection device configured to selectively couple and decouple an electronic device to the second set of electrodes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/378,107, filed Jul. 16, 2021, now U.S. Pat. No. 11,497,541, to beissued Nov. 15, 2022, which is a continuation of International PatentApplication No. PCT/US2020/061564, filed on Nov. 20, 2020, which is acontinuation-in part of U.S. patent application Ser. No. 16/689,967,filed on Nov. 20, 2019, now U.S. Pat. No. 11,065,047, granted Jul. 20,2021. U.S. patent application Ser. No. 17/378,107 is also acontinuation-in-part of U.S. patent application Ser. No. 16/689,967. Theentire disclosures of each of the above-referenced applications areincorporated herein by reference in their entirety.

TECHNICAL FIELD

The embodiments described herein relate generally to medical devices fortherapeutic electrical energy delivery, and more particularly tosystems, apparatuses, and methods for protecting electronic components(e.g., sensitive equipment or circuitry) during pulsed electric fieldablation procedures.

BACKGROUND

Application of brief ultra-short high voltage pulses to tissue maygenerate high electric fields in tissue to generate a local region ofablated tissue by the biophysical mechanism of irreversibleelectroporation. In applications including cardiac applications, highvoltage pulses may be applied in synchrony with a cardiac cycle of asubject. For example, high voltage pulses can be applied during specificperiods of the cardiac cycle (e.g., refractory cycle of the cardiacchambers), thereby avoiding the risk of induced arrhythmias such asventricular fibrillation. In some applications, to ensure synchrony ofpulsed field ablation pulses with the cardiac cycle, a cardiacstimulator can be used to pace or stimulate the cardiac chamber(s) witha regular cycle of periodic pacing signals having a well-defined timeperiod to establish periodicity of electrocardiogram (ECG) activity ofthe heart. Other devices, e.g., sensing and/or mapping systems,monitoring equipment or devices, can also be used to monitor a subject'scardiac cycle or detail a subject's cardiac activity. A cardiacstimulator may also be used in clinical procedures where a pacingfunction is required to maintain periodic and regular electricalactivity in the cardiac chambers during at least a portion of theprocedure. The cardiac stimulator and these other devices can useintracardiac devices (e.g., catheters) that can be suitably positionedin one or more cardiac chamber(s) to deliver signals to or receivesignals from the heart, or external surface patches or surface leads torecord patient surface ECG recordings. When these devices are usedduring a pulsed electric field ablation procedure, however, they canbecome exposed to high voltages. Such exposure can result in large,generally unbalanced, currents, and/or large common mode voltages withrespect to earth ground, being induced in the electrodes or leads of theintracardiac catheters. The large unbalanced currents and/or voltagescan span a band of frequencies and disrupt the operation of the cardiacstimulator and/or these other devices, thus interrupting pacing,sensing, mapping, magnetic sensor operation, and/or pulsed fieldablation functions. The disruption may be due to a hardware response tothe voltages and currents, or due to the equipment actively monitoringthe patient for anomalous signals for safety reasons.

Accordingly, it can be desirable to have systems, apparatuses, andmethods for addressing this issue.

SUMMARY

Described herein are systems, devices, and methods for protectingelectronic components (e.g., circuitry, devices, and/or othercomponents) from induced currents and high voltage exposure duringpulsed electric field ablation procedures.

In some embodiments, the ablation devices used in these systems may bedeployed epicardially or endocardially in cardiac applications. Thepulse waveforms delivered by the ablation devices may includepredetermined parameters or may be automatically generated by a signalgenerator.

In some embodiments, a system can include a first set of electrodes anda second set of electrodes. Generally, the second set of electrodes canbe disposed near cardiac tissue of a heart, or they can be part ofsurface patches or similar external recording or monitoring devices. Asignal generator may be configured to generate a pulse waveform. Thesignal generator may be coupled to the first set of electrodes and insome embodiments can be configured to repeatedly deliver the pulsewaveform to the first set of electrodes in synchrony with a set ofcardiac cycles of the heart. In other embodiments, the signal generatorcan be configured to repeatedly deliver the pulse waveform to the firstset of electrodes without synchrony being established with the cardiaccycle. In this latter case, it can still be useful to protect otherelectronic components (e.g., lab equipment such as cardiac stimulators(used generally for pacing functions), mapping systems, magnetictracking equipment, imaging equipment, etc.). The first set ofelectrodes may be configured to generate a pulsed electric field inresponse to the delivery of the pulse waveform to ablate the cardiactissue. A protection device may be configured to selectively couple anddecouple an electronic device to the second set of the electrodes. Acontrol element (e.g., processor, switch, control signal) may be coupledto the protection device and configured to control the protection deviceto decouple the electronic device from the second set of electrodesduring intervals of time beginning before and ending after each deliveryof the pulse waveform to the first set of electrodes.

In some embodiments, an apparatus may include a first set of electrodesdisposable near cardiac tissue of a heart. A signal generator may becoupled to the first set of electrodes and configured to generate apulse waveform. A switch component may be coupled to the signalgenerator. The switch component may be configured to switch between aconducting state in which an electronic device is coupled to a secondset of electrodes and a non-conducting state in which an electronicdevice is decoupled from the second set of electrodes. The second set ofelectrodes may be disposable near the first set of electrodes, orgenerally in a cardiac or anatomical chamber, or it may be disposed onor near the external surface of the subject. A processor may be coupledto the switch component. The processor may be configured to receivetrigger signals, each trigger signal associated with a cardiac cycle ofthe heart or with an ablation output from the signal generator. Inresponse to receiving each trigger signal, the processor may beconfigured to set the switch component to the non-conducting state suchthat the electronic device is decoupled from the second set ofelectrodes. The processor may be configured to deliver, from the signalgenerator and after setting the switch component to the non-conductingstate, the pulse waveform to the first set of electrodes such that thefirst set of electrodes generates a pulsed electric field. The processormay be configured to set, after delivering the pulse waveform, theswitch component to the conducting state such that the electronic deviceis coupled to the second set of electrodes. In some embodiments, acontrol signal being coupled to the switch component can set the stateof the switch to perform the functions described above.

In some embodiments, a method may include delivering pacing signals to aheart by a second set of electrodes positioned near cardiac tissue ofthe heart. After delivery of each pacing signal to the heart, the switchcomponent being selectively able to couple to an electronic device maybe set to be in a non-conductive state such that the second set ofelectrodes is decoupled from the electronic device. After setting theswitch component to be in the non-conductive state, a pulse waveform maybe delivered to a first set of electrodes positioned near cardiac tissueof the heart such that the first set of electrodes generates a pulsedelectric field for ablating the cardiac tissue. After delivering thepulse waveform, the switch component may be set to be in a conductivestate such that the second set of electrodes is coupled to theelectronic device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of components of a signal generator and acardiac stimulator being disposed in a heart, according to embodiments.

FIG. 2 is a schematic diagram of components of a signal generator and acardiac stimulator being disposed in a heart, with passive filtering forprotection of the cardiac stimulator, according to embodiments.

FIG. 3A is a schematic diagram of a system for protecting electroniccomponents from high voltage signals, according to embodiments.

FIG. 3B is a schematic diagram of a system for protecting electroniccomponents from high voltage signals, according to embodiments,including externally and/or internally disposed electrodes that may beconnected to a variety of medical equipment, including but not limitedto cardiac stimulators, ECG recording systems, ECG or other patient datamonitoring systems, electroanatomical mapping systems, devicenavigation/tracking systems, other monitoring systems and devices,combinations thereof, and the like.

FIG. 4 is a schematic diagram of components of a signal generator andone or more pieces of medical electronic equipment connected toelectrodes disposed in a heart/cardiac anatomy or on a patient surface,with a protection device for protection of the medical electronicequipment, according to embodiments.

FIG. 5 is a circuit diagram of a protection device for protectingelectronic components from high voltage signals, according toembodiments.

FIG. 6A illustrates a method for protecting electronic components fromhigh voltage signals, according to embodiments.

FIG. 6B illustrates a method for protecting electronic components fromhigh voltage signals for asynchronous delivery of ablation, according toembodiments.

FIG. 7A illustrates a time sequence of a cardiac pacing signal, energydelivery, and device isolation, according to embodiments. FIG. 7Billustrates a time sequence of a cardiac pacing signal, cardiacactivity, energy delivery, and device isolation, according toembodiments.

FIG. 8 is a schematic diagram of a system for protecting electricalcomponents from high voltage signals, according to embodiments.

FIG. 9 illustrates a time sequence of a cardiac pacing signal, cardiacactivity, energy delivery, and device isolation, according toembodiments.

FIGS. 10A-10E are block diagrams of alternative arrangements of aprotection device and a high voltage generator, according toembodiments.

FIG. 11 is a schematic diagram of a protection device for controllingconnections between electronic components operating in a high voltageexposure area, according to embodiments.

FIG. 12 is a schematic diagram of a system for protecting electroniccomponents from high voltage signals, according to embodiments.

FIG. 13 illustrates a time sequence of a cardiac pacing signal, cardiacactivity, energy delivery, and device isolation, according toembodiments.

FIG. 14 is a schematic diagram of a protection device for controllingconnections between electronic components operating in a high voltageexposure area, according to embodiments.

FIG. 15 is a schematic diagram of a protection device for controllingconnections between electronic components operating in a high voltageexposure area, according to embodiments.

FIG. 16 is a schematic diagram of a protection device for controllingconnections between electronic components operating in a high voltageexposure area, according to embodiments.

FIGS. 17A and 17B illustrate time sequences of a cardiac pacing signal,cardiac activity, energy delivery, and device isolation, according toembodiments.

FIG. 18 is a schematic diagram of a protection device for controllingconnections between electronic components operating in a high voltageexposure area, according to embodiments.

FIG. 19 is a schematic diagram of a system for protecting electricalcomponents from high voltage signals, according to embodiments.

FIG. 20A is a illustrates a time sequence of a signal connection andenergy delivery, according to embodiments.

FIG. 20B is a illustrates a time sequence of a signal connection andenergy delivery, according to embodiments.

FIG. 20C is a illustrates a time sequence of a signal connection andenergy delivery, according to embodiments.

DETAILED DESCRIPTION

Described herein are systems, devices, and methods for protectingcircuits from high power noise induced during pulsed electric fieldablation. Pulsed electric field ablation uses ultra-short high-voltagepulses to generate large electric fields at desired regions of interestto generate a local region of ablated tissue via irreversibleelectroporation. In certain applications, including cardiacapplications, it can be desirable to generate pulses for pulsed electricfield ablation in synchronicity with a cardiac cycle. Synchronizingablation energy delivery with the cardiac cycle may reduce the risk ofinduced arrhythmias such as atrial and/or ventricular fibrillation. Onemethod of synchronizing delivery of pulses can be to pace or stimulateone or more cardiac chambers with periodic pacing signals with apredefined time period. For example, a cardiac stimulator may be used todeliver pacing pulses to one or more cardiac chambers such that thecardiac rhythm of a patient synchronizes with the pacing pulse.

In some embodiments, pacing pulses can be delivered to the cardiacchamber(s) via an intracardiac catheter that is suitably positioned inthe chamber(s). For example, FIG. 1 depicts a cardiac stimulator (28)that is coupled to an intracardiac catheter (30) suitable positioned ina chamber of a heart (2). The catheter (30) can have one or moreelectrodes (32, 34) that are used to conduct a pacing signal into theheart. In an embodiment, a pair of electrodes on the catheter (30)(e.g., a most distal electrode (32) and an electrode (34) immediatelyproximal to the most distal electrode (32)) can be used as a bipolarpair to deliver the pacing signal, thus providing forward and returncurrent paths for the pacing signal. The cardiac chamber responds to thepacing pulse (referred to herein as “pacing capture”) by timing its ECGsignal generation (e.g., the QRS waveform) to synchronize with thepacing pulse. Accordingly, periodicity of the ECG activity of the heartcan be established. Once such periodicity is established and confirmedby the physician (e.g., from displayed ECG activity obtained, forexample, for a variety of recording or sensing electrodes), the deliveryof the pulsed field ablation pulses can be timed to start in synchronywith the pacing pulses, including any predetermined offsets, anddelivery can be completed within refractory windows following the QRSwaveform of an ECG signal.

In cardiac applications, pulsed field ablation energy can be deliveredthrough a customized ablation catheter including a plurality ofelectrodes. For example, as depicted in FIG. 1 , a signal generator (22)(e.g., a pulsed field ablation pulse generator) can be coupled to anablation catheter (10) with electrodes (12) that are suitably disposedin the heart (2). The delivery of the pulsed field ablation voltagepulses can be synchronized with the delivery of the pacing signals withappropriate offsets, as indicated by (60). Since the pacing catheter(30) can be located in the cardiac environment as well (e.g., in thesame or a nearby chamber of the heart (2)), high voltage pulse waveformsapplied to heart tissue may couple to the pacing catheter (30) andinduce currents in one or more of the pacing catheter (30) and devicescoupled thereto (e.g., cardiac stimulator (28)).

During normal delivery of pacing pulses, the forward and return currentsof the electrodes (32, 34) of the pacing catheter (30) are balanced(e.g., equal in magnitude and opposite in direction). However,electrical coupling of the high voltage ablation energy to the pacingcatheter (30) may induce large and generally unbalanced currents and/orcommon mode voltages in the leads of the pacing catheter (30). Theselarge unbalanced currents and/or voltages can span a band of frequenciesand can disrupt the operation of the pacing system or cardiac stimulator(28) or other electronic equipment coupled thereto. For example, thelarge voltage exposure of the pacing catheter (30) may exceed thecommon-mode rejection of the cardiac stimulator (28) and cause systemfailure and/or reset of the stimulator (which can be either pacing forsynchronized delivery of ablation or pacing the cardiac chamber(s) forother medical reasons). The high voltage levels and high currentsassociated with the induced noise imply a large power level for thenoise and can lead to unwanted effects.

This high-power induced noise can be difficult to suppress and,therefore, it can be desirable to have systems, devices, and methods forsuppressing induced currents in accessory devices in pulsed electricfield ablation energy delivery applications. In some embodiments,currents induced by pulsed electric field ablation can be suppressedthrough implementation of passive filtering systems, devices, andmethods, as described in U.S. Application Ser. No. 62/667,887, filed onMay 7, 2018, and titled “SYSTEMS, APPARATUSES, AND METHODS FOR FILTERINGHIGH VOLTAGE NOISE INDUCED BY PULSED ELECTRIC FIELD ABLATION,” thecontents of which are hereby incorporated by reference in its entirety.FIG. 2 depicts an example of a system including passive filtering. Acardiac stimulator (28′) can be coupled to a pacing catheter (30′)including a plurality of electrodes (32′, 34′). A signal generator (22′)can be coupled to an ablation catheter (10′) including a plurality ofelectrodes (12′). The electrodes (32′, 34′) of the pacing catheter (30′)can be disposed in a heart (2′) along with the electrodes (12′) of theablation catheter (10′). A filter element (50′) can be coupled betweenthe cardiac stimulator (28′) and the pacing catheter (30′). The filterelement (50′) can passively filter signals from the pacing catheter(30′) prior to those signals being received at the cardiac stimulator(28′), thereby suppressing certain induced currents. For example, at A,long wires can pick up high voltages, while at B, after the passivefiltering, residual voltage and current can pass onto the cardiacstimulator (28′).

In some instances, however, coupled noise having a large amplitude(e.g., large voltage spikes) can be difficult to reject using passivefiltering techniques and therefore faults and/or resets of equipmentincluding a cardiac stimulator can still occur. Commercially availablestimulators can also include different design parameters such that onelevel of protection may be sufficient for one type of stimulator whilebeing insufficient for a second type of stimulator.

Systems, devices, and methods disclosed herein provide protection forsensitive electronics and ancillary devices in pulsed electric fieldablation applications using actively driven rapid switching of signalpaths. In some embodiments, a protection device may be coupled to thepacing device to actively and selectively electrically isolate thepacing device from the other electronic components of the ablationsystem. In particular, the pacing device may be electrically isolatedfrom the system during a predetermined time period corresponding todelivery of the pulse waveform to tissue. Electrical connection may bereestablished to enable operation of the pacing device between periodsof high voltage energy delivery. In some embodiments, the protectiondevice may include a high speed switch coupled between the ablationsystem and pacing device. Consequently, components of the system such asthe cardiac stimulator may be protected from currents that may beinduced in the pacing device by the high voltage pulse waveforms appliedby the ablation device. Additionally or alternatively, the protectiondevice may further provide passive circuit protection.

In some embodiments, sensitive circuitry or a piece of ancillaryequipment (e.g., a cardiac stimulator, electroanatomical mapping system,ECG recording or monitoring system, etc.) can be protected from highvoltage pulsed field ablation signals present in a subject by havingsuch circuitry or equipment be electrically isolated. Electricalisolation can be implemented manually by disconnecting conductorsbetween the circuitry or equipment can the subject, but a manualapproach may not be possible in certain instances. For example, forcertain types of equipment that serve repeated function, e.g., a cardiacstimulator that is intended to provide ongoing pacing of a subject'sheart during a pulsed field ablation procedure, it is necessary forphysical connections between the equipment and the subject to remainintact. In these instances, it can be desirable to accomplish physicaldisconnection using electronic components. For example, electroniccomponents can be used to provide bi-directional open circuit isolationbetween the subject and protected ancillary equipment for certain timeintervals during which a high voltage is present and re-establishconnections during other time intervals to otherwise allow for intendedfunctioning of the equipment.

The term “electroporation” as used herein refers to the application ofan electric field to a cell membrane to change the permeability of thecell membrane to the extracellular environment. The term “reversibleelectroporation” as used herein refers to the application of an electricfield to a cell membrane to temporarily change the permeability of thecell membrane to the extracellular environment. For example, a cellundergoing reversible electroporation can observe the temporary and/orintermittent formation of one or more pores in its cell membrane thatclose up upon removal of the electric field. The term “irreversibleelectroporation” as used herein refers to the application of an electricfield to a cell membrane to permanently change the permeability of thecell membrane to the extracellular environment. For example, a cellundergoing irreversible electroporation can observe the formation of oneor more pores in its cell membrane that persist upon removal of theelectric field.

Pulse waveforms for electroporation energy delivery as disclosed hereinmay enhance the safety, efficiency, and effectiveness of energy deliveryto tissue by reducing the electric field threshold associated withirreversible electroporation, thus yielding more effective ablativelesions with a reduction in total energy delivered. In some embodiments,the voltage pulse waveforms disclosed herein maybe hierarchical and havea nested structure. For example, the pulse waveform may includehierarchical groupings of pulses having associated timescales. In someembodiments, the methods, systems, and devices disclosed herein maycomprise one or more of the methods, systems, and devices described inInternational Application Serial No. PCT/US2019/014226, filed on Jan.18, 2019, published as International Publication No. WO/2019/143960 onJul. 25, 2019, and titled “SYSTEMS, DEVICES AND METHODS FOR FOCALABLATION,” the contents of which are hereby incorporated by reference inits entirety.

Systems and Devices

Disclosed herein are systems and devices configured for suppressinginduced currents in connection with tissue ablation. Generally, a systemdescribed here for ablating tissue with high voltage pulse waveforms mayinclude a cardiac stimulator for generating a cardiac pacing signaldelivered by a pacing device to the heart. The cardiac pacing signal isused to synchronize delivery of a pulse waveform generated by a signalgenerator, and the pulse waveform is delivered using an ablation devicehaving one or more electrodes. In another embodiment, the ablation withhigh voltage pulse waveforms can be performed asynchronously (i.e.,without synchronizing with cardiac stimulation). It is generallydesirable in these embodiments also to protect other electronicequipment such as cardiac stimulators, electroanatomical mappingsystems, device navigation/tracking systems, ECG recording or monitoringsystems etc. that may be connected to the patient via device electrodesthat are placed either internally in the patient or externally on thepatient or attached to the patient surface (for example, needleelectrodes, pacing leads etc.). Thus, the systems, methods andimplementations described in the present disclosure apply toasynchronous ablation delivery. Furthermore, as described herein, thesystems and devices may be deployed epicardially and/or endocardially totreat atrial fibrillation. Voltages may be applied to a selected subsetof the electrodes, with independent subset selections for anode andcathode electrode selections.

FIG. 3A illustrates an example system (1700) including an integratedprotection element (1750). The protection element (1750) can be situatedbetween electrical components (1730) and a target area (TA) (e.g., aheart of a patient). The protection element (1750) can be configuredwith a voltage rating corresponding to an anticipated exposure voltageon the patient side of a pulsed electric field ablation procedure, whichcan be a few thousand volts. The protection element (1750) can functionas an isolation component that is configured to transition to an opencircuit configuration and back to a closed circuit configuration basedon a control signal. The protection element (1750) is configured torespond quickly (e.g., quickly switch between its open and closedconfigurations) to reduce the open-circuit duty cycle, such that theprotection element (1750) can electrically isolate certain electricalcomponents (1730) (e.g., monitoring equipment or devices, cardiacstimulators, etc.) for the duration of a high-voltage exposure butotherwise connect those electrical components to the target area (TA).

Examples of suitable protection elements (1750) includeelectro-mechanical relays (e.g., reed relays), solid-state relays,and/or high-voltage metal-oxide semiconductor field-effect transistor(MOSFET) devices. Reed relays can be a less suitable option forisolation component implementation, as such relays act slower than othertypes of protection devices and are susceptible to damage/contact fusingif switched during exposure to high currents. When the system (1700) isused with the protection element (1750) implemented as a reed relay, thecoordination and timing of the system (1700) need to be adjusted tohandle the slower reaction time of such relays. A preferredimplementation of a protection element (1750) is with two back-to-backMOSETs with common source terminals, as further described with referenceto FIG. 5 below.

FIG. 3B illustrates an example system (1800) including an integratedprotection element (1805). The protection element (1805) can be situatedbetween electrical components (1801) and patient anatomy (1808). Theprotection element (1805) can be configured with a voltage ratingcorresponding to an anticipated exposure voltage on the patient side ofa pulsed electric field ablation procedure, which can be a few thousandvolts. Such high voltage exposure can occur via internally placed (withrespect to patient) device electrodes or sensors (1819) or externallyplaced/mounted (on the patient surface) electrodes or sensors (1821).Such electrodes or sensors in general can connect to a variety ofmedical electronic equipment, including but not limited toelectroanatomical mapping systems, device navigation/tracking systems,ECG recording/monitoring systems, combinations thereof, and the likethat can generally be in use in a clinical laboratory or procedure room.In the embodiments described herein, a sensor can be a generic sensorincluding a dedicated electromagnetic sensor, an electrode for receivingvoltage signals generated by a location tracking system, an electrodefor monitoring native cardiac electrical activity, and more generally asensor for sensing electrical signals of various types. The protectionelement (1805) can function as an isolation component that is configuredto transition to an open circuit configuration and back to a closedcircuit configuration based on a control signal (1812). The protectionelement (1805) is configured to respond quickly (e.g., quickly switchbetween its open and closed configurations) to reduce the open-circuitduty cycle, such that the protection element (1805) can electricallyisolate electrical components (1801) such as those described above forthe duration of a high-voltage exposure but otherwise connect thoseelectrical components to the patient anatomy (1808).

Examples of suitable protection elements (1805) includeelectro-mechanical relays (e.g., reed relays), solid-state relays,and/or high-voltage metal-oxide semiconductor field-effect transistor(MOSFET) devices. Reed relays can be a less suitable option forisolation component implementation, as such relays act slower than othertypes of protection devices and are susceptible to damage/contact fusingif switched during exposure to high currents. When the system (1800) isused with the protection element (1805) implemented as a reed relay, thecoordination and timing of the system (1800) need to be adjusted tohandle the slower reaction time of such relays. In some embodiments, aprotection element (1805) can include two back-to-back MOSFETs withcommon source terminals, as further described with reference to FIG. 5below.

FIG. 4 is a schematic diagram of an electroporation system disposed in aheart (202) of a patient (200). The electroporation system may includean ablation device (210), signal generator (222), electricalcomponent(s) (e.g., medical electronic equipment or devices) (228),catheter device (230), and protection device (e.g., protection circuit)(250). In some embodiments, the electrical component(s) (228) may beimplemented as a cardiac pacing system. The signal generator (222) maybe coupled to the ablation device (210) and configured to receive apacing/synchronization signal (260) generated by the cardiac pacingsystem. The signal generator (222) may be configured to generateablation pulse waveforms delivered to tissue by electrodes (212) of theablation device (210). In some embodiments, the catheter device (230)implemented as a pacing device (230) may be configured to pace the heartand measure cardiac activity using respective pacing electrodes (232)and signal electrodes (234). In some embodiments, the electricalcomponent(s) (228) can be implemented as monitoring equipment or devicesthat can be coupled to one or more sensors (e.g., electrodes) (232, 234,271) for measuring physiological data of a patient. In some embodiments,sensors (e.g., electrodes (271)) may be placed externally at the patientsurface. The protection device (250) may be coupled between theelectrical component(s) (228) and the electrodes (232, 234) of thecatheter device (230) or electrodes (271). In some embodiments, theprotection device (250) is configured to synchronize electricalisolation of the pacing device (230) with delivery of ablation energy bythe ablation device (210).

In some embodiments, a distal portion of an ablation device (210) may beintroduced into an endocardial space of the heart (202) (e.g., a leftatrium), e.g., through an atrial septum via a trans-septal puncture. Thedistal portion of the ablation device (210) may include a set ofelectrodes (212) configured to deliver ablation energy (e.g., pulseelectric field energy) to tissue. For example, the ablation device (210)may be positioned near an inner radial surface of a lumen (e.g., one ormore pulmonary vein ostia) (not shown) for delivery of pulse waveformsto ablate tissue. In some embodiments, the electrodes (212) of theablation device (216) may be a set of independently addressableelectrodes. Each electrode may include an insulated electrical leadconfigured to sustain a voltage potential of at least about 700 Vwithout dielectric breakdown of its corresponding insulation. In someembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200 V to about 3,000V across its thickness without dielectric breakdown. In someembodiments, the set of electrodes may include a plurality ofelectrodes. The plurality of electrodes may be grouped into one or moreanode-cathode subsets such as, for example, a subset including one anodeand one cathode, a subset including two anodes and two cathodes, asubset including two anodes and one cathode, a subset including oneanode and two cathodes, a subset including three anodes and one cathode,a subset including three anodes and two cathodes, and/or the like.

The signal generator (222) may be configured to generate ablation pulsewaveforms for irreversible electroporation of tissue, such as, forexample, pulmonary vein ostia. For example, the signal generator (222)may be a voltage pulse waveform generator and deliver a pulse waveformto the ablation device (210).

In some embodiments, the signal generator (222) is configured togenerate the ablation pulse waveform in synchronization with theindication of the pacing signal (e.g., within a common refractorywindow). For example, in some embodiments, the common refractory windowmay start substantially immediately following a ventricular pacingsignal (or after a very small delay) and last for a duration ofapproximately 250 milliseconds (ms) or less thereafter. In suchembodiments, an entire pulse waveform may be delivered within thisduration.

The protection device (250) may be coupled between the electricalcomponents (228) and the catheter device (230). As described in moredetail herein, a control signal (also referred to herein as a protectionsignal) may be generated to synchronize operation of the protectiondevice (250) with the generation of the pulse waveform by the signalgenerator (222). The protection device (250) may be configured toreceive the control signal to control a state of the electricalconnection between the catheter device (230) and the electricalcomponents (228). For example, the protection device (250) may beconfigured to form an open circuit between the electrical components(228) and the catheter device (230) at least during delivery of ablationenergy by the ablation device (210). Otherwise, the protection device(250) may be configured to electrically couple the pacing device (230)with the electrical components (228). In some embodiments, theprotection device (250) may be configured to provide bi-directional opencircuit isolation during high energy ablation energy delivery. In someembodiments, the protection device (250) may be formed separate from theelectrical components (228) and/or the catheter device (230), and inother embodiments, the protection device (250) can be integrated intoone or more electrical components (228) and/or catheter device (230). Insome embodiments, the protection device (250) may include one or more ofan internal power source (e.g., battery) and a power connector to coupleto an external power source (e.g., medical grade power supply,wall-outlet). An internal power source may reduce ground noiseinjection.

In some embodiments, the electrical components (228), the protectiondevice (250), and/or the signal generator (220) may be in communicationwith one another, e.g., for coordinating timing of the pulse waveformdelivery, pacing signal delivery, and/or protection device controlsignal delivery. In some embodiments, the protection device (250),and/or the signal generator (220) may be in communication with oneanother, e.g., for coordinating timing of the pulse waveform delivery,pacing signal delivery, and/or protection device control signaldelivery. In some embodiments, the protection device (250) may beintegrated with the signal generator (222) in a single console.

In some embodiments, the electrical components (228), the protectiondevice (250), and/or the signal generator (220) may be in communicationwith other devices (not shown) via, for example, one or more networks,each of which may be any type of network. A wireless network may referto any type of digital network that is not connected by cables of anykind. However, a wireless network may connect to a wireline network inorder to interface with the Internet, other carrier voice and datanetworks, business networks, and personal networks. A wireline networkis typically carried over copper twisted pair, coaxial cable or fiberoptic cables. There are many different types of wireline networksincluding, wide area networks (WAN), metropolitan area networks (MAN),local area networks (LAN), campus area networks (CAN), global areanetworks (GAN), like the Internet, and virtual private networks (VPN).Hereinafter, network refers to any combination of combined wireless,wireline, public and private data networks that are typicallyinterconnected through the Internet, to provide a unified networking andinformation access solution. The system (100) may further comprise oneor more output devices such as a display, audio device, touchscreen,combinations thereof, and the like.

The electrical components (228), the protection device (250), and/or thesignal generator (220) can include one or more processor(s), which canbe any suitable processing device configured to run and/or execute a setof instructions or code. The processor may be, for example, a generalpurpose processor, a Field Programmable Gate Array (FPGA), anApplication Specific Integrated Circuit (ASIC), a Digital SignalProcessor (DSP), and/or the like. The processor may be configured to runand/or execute application processes and/or other modules, processesand/or functions associated with the system and/or a network associatedtherewith (not shown). The underlying device technologies may beprovided in a variety of component types, e.g., metal-oxidesemiconductor field-effect transistor (MOSFET) technologies likecomplementary metal-oxide semiconductor (CMOS), bipolar technologieslike emitter-coupled logic (ECL), polymer technologies (e.g.,silicon-conjugated polymer and metal-conjugated polymer-metalstructures), mixed analog and digital, and/or the like.

The electrical components (228), the protection device (250), and/or thesignal generator (220) can include one or more memory or storagedevice(s), which can be, for example, a random access memory (RAM), amemory buffer, a hard drive, an erasable programmable read-only memory(EPROM), an electrically erasable read-only memory (EEPROM), a read-onlymemory (ROM), Flash memory, etc. The memory may store instructions tocause the processor of any one of the electrical components (228), theprotection device (250), and/or the signal generator (220) to executemodules, processes and/or functions, such as pulse waveform generation,isolation/protection, and/or cardiac pacing.

While FIG. 4 depicts a system including electrical components (228) thatare separate from the signal generator (220), in some embodiments, oneor more electrical components (228) may form a part of and/or beintegrated into signal generator (222). In some embodiments, one or moreelectrodes (212, 232, 234) may function as sensing electrodes.

FIG. 5 is a circuit diagram of a protection device (300) including afirst MOSFET (310) and a second MOSFET (320). The MOSFETs (310, 320) canbe arranged as back-to-back MOSFETs with common source terminals suchthat the body diodes of the MOSFETs (310, 320) are in opposingdirections. Such an arrangement can provide bi-directional isolationwith precise timing control. The MOSFETs (310, 320) can be driven byisolated gate-drive circuits (330, 340). Specifically, the first MOSFET(310) can be coupled to a first gate driver (330), and the second MOSFET(320) can be coupled to a second gate driver (340). The first and secondgate drivers (330, 340) may be coupled to a coupling (350) (e.g., anisolation/optical coupling) that can receive a control signal 352. Theprotection device (300) may be configured to reduce high voltagecoupling of connected devices. For example, the protection device (300)may be configured to withstand voltages of up to about 3,000 V deliveredby an ablation device. The protection device (300) may be configured totransition between a closed-circuit configuration and an open-circuitconfiguration based on a received protection signal (352) (e.g., controlsignal) such that the protection device (300) is in an open-circuitconfiguration for the duration of high-voltage ablation energy deliveryand in a closed-circuit configuration at other times, e.g., to enabledelivery of a pacing signal.

The protection devices described herein can be a separate piece ofequipment or can be integrated into ancillary equipment or a pulsedfield ablation stimulator. FIGS. 10A-10E are block diagrams of a set ofsystems including protection devices, both integrated with and separatefrom other system components. In FIGS. 10A-10E, the protection devicescan include components that are structurally and/or functionally similarto any of the other protection devices described herein (e.g.,protection devices depicted in FIGS. 3A, 3B, 4, 5, 8, 11, 12, 14-16, 18,and 19 ). FIG. 10A illustrates a signal generator (800) (e.g., forpulsed electric field ablation) comprising a protection device (810)integrated therewith. For example, one or more of the signal generator(800), protection device (810), electrical components (e.g., electricalcomponents (228) including, for example, monitoring equipment, a cardiacstimulator, etc.), and signal analyzer (e.g., signal detector (670)) maybe integrated into a single enclosure (e.g., housing, signal generatorconsole). This may allow sensitive electronic circuitry to be protectedwithin the same enclosure from high voltage noise. External electricalcomponents (e.g., ancillary equipment) may be similarly protected bycoupling such components to the protection device (810) at a pointfurther downstream from the high voltage exposure point (e.g., thepatient). For example, external equipment can be protected by routingsignals received by the system through the protection device (810)before having those signals reach the patient, such that the protectiondevice (810) can time its blanking interval to coincide with times ofpotential high voltage exposure. With the integrated configurationdepicted in FIG. 10A, a digital “blanking” signal (e.g., control signal)can be provided to the protection device by the signal generator (800)to indicate the necessary time for isolation (e.g., protection) ofsensitive electronic components. The “blanking” signal may be configuredto control the protection device to electrically isolate a set ofelectronic components internal and external to the signal generator(800), thereby providing coordinated and robust protection.

In some embodiments, manually operated switches can be configured to bea protection device to protect electronic components or equipment fromablation-induced noise.

In some embodiments, the signal generator and protection device may beseparate pieces of equipment (e.g., formed in different enclosures). Insuch embodiments, control signals can be transmitted between the signalgenerator and protection device via wired or wireless communications;however, wired control signals can be more robust and avoid the risk ofdelay more often associated with wireless communications. With anexternal or separate protection device, the protection device can beeither battery-powered or wall-powered, e.g., using medical gradeisolation, but battery-powered protection devices can be more desirableto reduce ground noise injection into the patient from isolated wallpower supplies. FIG. 1013 illustrates a signal generator (800) coupledto a protection device (810) via a wired connection (820) (e.g.,power/data cable). FIG. 10C illustrates a signal generator (800) coupledto a protection device (810) via a wireless connection. For example, theprotection device (810) may comprise a wireless transceiver (830)configured to receive a control signal (e.g., transmitted from thesignal generator (800)).

In embodiments where the protection device is implemented independentlyfrom the signal generator (e.g., pulsed field ablation generator), theprotection device requires a mechanism for synchronizing with deliveryof high voltages pulses such that it can effectively isolate certainelectronic components during such delivery. In some embodiments, aprotection signal may synchronize electrical isolation of certainelectronic components (e.g., a stimulator) with delivery of ablationenergy to tissue based on one or more of a timed-trigger pulse from astimulator, stimulation-pulse sensing (e.g., of stimulation pulses forcardiac capture), measured cardiac activity (e.g., R-wave detection,and/or high-voltage sensing (e.g., with rapid application of isolationupon detection of a high voltage spike on a patient side). Such isfurther described below with reference to FIG. 12 . FIGS. 10D and 10Eillustrate two configurations of implementing synchronization. Suchconfigurations are similar to those described with respect to FIGS. 7A-9. FIG. 10D illustrates a signal generator (800) and a protection device(810), both configured to receive signals from a cardiac stimulator(840). The cardiac stimulator (840) may be configured to synchronizeablation energy delivery by the signal generator (800) and electricalisolation by the protection device (810) through output of respectivesignals (e.g., a trigger or control signal) to the signal generator(800) and the protection device (810). FIG. 10E illustrates a signalgenerator (800) and a protection device (810) both coupled to a patient(850) and configured to operate in synchronicity with one another basedon measured data (e.g., cardiac stimulation or pacing pulse, R-wavedetection, high voltage detection). When implementing synchronizationbased on stimulation pulse detection, a sufficiently high predeterminedthreshold (e.g. 5 V) can be set to reduce the likelihood offalse-positive sensing, which can undesirably lead to increasedoccurrences of isolation and disconnection of protected electricalcomponents from a patient.

Protection devices as described herein can be configured to isolate aplurality of electrical components (e.g., sensitive circuitry orequipment) from high voltages and induced currents. FIG. 11 is a blockdiagram of a system (910) coupled to a patient (900). One or moredevices of the system (910) (e.g., pacing device, catheters, stylets,probes, electrodes, etc.) may be coupled to the patient (900) and may besusceptible to induced current from high voltage ablation energydelivery. Each of the devices of the system (910) may be coupled to aprotection device (920) configured to selectively electrically isolateelectrical components disposed downstream from the protection device(920) from those portions of devices disposed in the heart and areexposed to the high voltages. The protection device (920) can includecomponents that are structurally and/or functionally similar to any ofthe other protection devices described herein (e.g., protection devicesdepicted in FIGS. 3A, 3B, 4, 5, 8, 10A-10E, 12, 14-16, 18, and 19 ). Insome embodiments, a single protection signal (924) may be configured tocontrol the protection device (920) and provide electrical isolation,e.g., through protection elements implemented as a plurality of switches(922), of the plurality of electronic component(s) simultaneously. Insome embodiments, one or more of the switches (922) can includeelectro-mechanical relays (e.g., reed relays), solid-state relays,and/or MOSFET devices. For example, one or more of the switches (922)can include two back-to-back MOSFETs with common source terminals, asdepicted in FIG. 5 .

In some embodiments, e.g., where a protection device is implemented asan independent system without signals being communicated from a highvoltage pulse generator (e.g., for pulsed field ablation), the operationof the protection device can be synchronized based on stimulation-pulsesensing, trigger pulses from a cardiac stimulator, R-wave sensing, orhigh-voltage sensing. FIG. 12 is a schematic diagram of anelectroporation system disposed in a heart (1002) of a patient (1000)that includes an ablation device (1010), signal generator (1022),cardiac stimulator (1028), pacing device (1030), and protection device(1050). The signal generator (1022) may be coupled to the ablationdevice (1010). The signal generator (1022) may be configured to generatepulse waveforms delivered to electrodes (1012) of the ablation device(1010) for generating a pulsed electric field for ablation. The pacingdevice (1030) may be configured to pace the heart (1002) using pacingelectrodes (1032, 1034) and/or measure cardiac activity of the heart(1002) (e.g., electrocardiogram) using one or more electrodes (e.g.,electrodes (1032, 1034) or other electrodes (not depicted)). Theprotection device (1050) may be coupled between the cardiac stimulator(1028) and the pacing device (1030). The protection device (1050) caninclude components that are structurally and/or functionally similar toany of the other protection devices described herein (e.g., protectiondevices depicted in FIGS. 3A, 3B, 4, 5, 8, 10A-10E, 11, 14-16, 18, and19 ).

In some embodiments, the protection device (1050) may be configured tosynchronize electrical isolation of the cardiac stimulator (1028) withpulse waveform delivery by the ablation device (1010) based on one ormore signals. The protection device (1050) may be synchronized based onthe same signal or combination of signals as the signal generator (1022)or independently based on one or more of a stimulation signal (1060)from the cardiac stimulator (1028) (which can also be sent to the signalgenerator (1022)), measured data (e.g., stimulation-pulse detectionsignal (1070), R-wave detection signal (1090), and high-voltagedetection signal (1092)), and a signal generator signal (1080). Inalternative embodiments, the protection device (1050) and the signalgenerator (1022) can be activated based on different signals or adifferent combination of signals. For instance, the protection device(1050) may be controlled based on a cardiac pacing signal (1060) andpulse waveform delivery may be based on a detected R-wave signal (1090).In embodiments using stimulation pulse sensing, the sensing can beimplemented with a predetermined threshold (e.g., about 5V) in order toreduce false-positives that may increase the number of disconnectionsbetween the cardiac stimulator (1028) and/or other protected electroniccomponents and the patient (1000). To provide another layer of safety, aprotection device for any external electronic components can beconfigured to provide a low-impedance connection between the protectedelectronic components and the patient when unpowered. FIG. 14 is a blockdiagram of electrical component(s) (1210) (e.g., including sensitiveequipment or circuitry) coupled to a patient (1220) via a protectiondevice (1200). One or more electrical component(s) (1210) (e.g.,monitoring equipment, cardiac stimulator, such as any described herein)may be coupled to the patient (1220) and may be susceptible to inducedcurrent from high voltage ablation energy delivery. Each of theelectrical component(s) (1210) may be coupled to the protection device(1200) to selectively electrically isolate those components from devicesdisposed in the heart of the patient (1220). The protection device(1200) can include components that are structurally and/or functionallysimilar to any of the other protection devices described herein (e.g.,protection devices depicted in FIGS. 3A, 3B, 4, 5, 8, 10A-10E, 11, 12,15, 16, 18, and 19 ).

The protection device (1200) can be configured such that the electricalcomponent(s) (1210) are electrically coupled (e.g., through alow-impedance connection) to the patient (1220) when the protectiondevice (1200) is unpowered. This safety feature may allow for patientconnection by default and allow the electrical component(s) (1210) tooperate even if power is lost to the protection device (1200). Forexample, a cardiac stimulator (e.g., cardiac stimulator (28)) includedin the electrical component(s) (1210) may provide pacing to the patient(1220) when the protection device (1200) is powered off

A first signal (1202) (e.g., control signal) may be configured tocontrol the protection device (1200) and provide electrical isolationthrough a first switch (1206) as described herein. A second signal(1204) (e.g., a power signal) may be configured to control theprotection device (1200) through a second switch (1208). In someembodiments, the second switch (1208) may comprise a relay (e.g., reedswitch, or solid-state type switch) configured in parallel to the firstswitch (1206) used for isolation/blanking and configured to switch openwhen the protection device (1200) is powered. In some embodiments, thefirst switch (1206) can include an electromechanical relay (e.g., reedrelay), a solid-state relay, and/or a MOSFET device. For example, thefirst switch (1206) can include two back-to-back MOSFETs with commonsource terminals, as depicted in FIG. 5 . The second pathway providedvia the second switch (1208) can normally be set to a closed state toprovide the low-impedance connection between the electrical component(s)(1210) and the patient (1220).

FIG. 15 provides another example embodiment for a system including aprotection device (1300). Specifically, FIG. 15 is a block diagram ofelectrical component(s) (1310) coupled to a patient (1320) via aprotection device (1300). One or more electrical component(s) (1310)(e.g., monitoring equipment, cardiac stimulator) may be coupled to thepatient (1320) via the protection device (1300) configured toselectively electrically isolate those electrical components) (1310)from devices disposed in the heart of the patient (1320), e.g., via afirst signal (1302). The protection device (1300) can include componentsthat are structurally and/or functionally similar to any of the otherprotection devices described herein (e.g., protection devices depictedin FIGS. 3A, 3B, 4, 5, 8, 10A-10E, 11, 12, 14, 16, 18, and 19 ). In asimilar manner as described with respect to FIG. 14 , the electricalcomponent(s) (1310) may be electrically coupled to the patient (1320)when the protection device (1300) is unpowered via normally closedswitches that are disposed in parallel to the blanking/protectioncomponents. When power is provided to the protection device (1300), asignal (1304) corresponding to the power can open the normally closedswitches. In some embodiments, the protection device (1300) may includeadditional circuit protection and filtering functionality configured toreduce peak-to-peak voltages of high slew rate and/or high voltagesignals, even when the protection device (1300) is un-powered and/orwhen the electrical component(s) (1310) are not isolated from thepatient (1320). The protection device (1300) may include one or more ofa passive filter device (1330) (as described above with reference toFIG. 2 ), common mode protection device (1340), and differential/highvoltage protection device (1350), which may include one or more commonand differential mode chokes using ferrites/magnetics, inductor andcapacitor-based filters, and differential high voltage and differentialclamping components including one or more oftransient-voltage-suppression (TVS) diodes/tranzorbs, gas dischargetubes, and thyristors. In some embodiments, the methods, systems, anddevices disclosed herein may comprise one or more of the methods,systems, and devices described in U.S. Application Ser. No. 62/667,887,filed on May 7, 2018, and titled “SYSTEMS, APPARATUSES, AND METHODS FORFILTERING HIGH VOLTAGE NOISE INDUCED BY PULSED ELECTRIC FIELD ABLATION,”incorporated above in its entirety.

In some cardiac stimulators (e.g., electrophysiology laboratorystimulator systems), patient connections may be monitored for highimpedance to alert a user of disconnections. To prevent undesirablewarnings during use of a protection device (e.g., during blankingintervals), a fixed known impedance (e.g., by way of a fixed resistorhaving a value in a range expected by the stimulator such as, forexample, 1 kOhm) can be provided to the connections to the stimulator.FIG. 16 is a block diagram of electrical component(s) (1410) coupled toa patient (1420). One or more electrical component(s) (1410) (e.g.,monitoring equipment, cardiac stimulator) may be coupled to the patient(1420) via a protection device (1400) configured to selectivelyelectrically isolate such components from devices disposed in the heartof the patient (1420) via a signal (1402). The protection device (1400)can include components that are structurally and/or functionally similarto any of the other protection devices described herein (e.g.,protection devices depicted in FIGS. 3A, 3B, 4, 5, 8, 10A-10E, 11, 12,14, 15, 18, and 19 ).

A cardiac stimulator included in the electrical component(s) (1410) maycontinuously monitor the electrical connection to the patient (1420) andgenerate a disconnection signal (e.g., alarm signal to the user) whendisconnection (e.g., high-impedance) is detected. In some embodiments,in order to inhibit generation of a disconnection signal by the system(1410) during a protection interval of the protection device (1400), theprotection device (1400) may provide the cardiac stimulator with apredetermined impedance (1440) (e.g., between about 100 Ohm and about 10kOhms) in a range that the stimulator would expect to correspond tonormal operations. For example, the protection device (1400) operatingduring the protection interval may send a signal to close a switch inseries with a resistor (1440) that can then provide the fixed impedancevalue. The quick transition between “patient connection” and“open-circuit with fixed resistor load” can be sufficiently fast toprevent any warnings or alerts by the cardiac stimulator. In someembodiments it may be useful to switch-in the load to the electricalcomponent first, a short time interval before disconnecting the patientconnections (e.g., on the order of 1 us to 100 us). If this is done,there is not a small amount of time when the electrical component seesan open-circuit. The patient-connections can then be connected before(e.g., immediately before) the resistive load is disconnected. Anotherimplementation optimization is to provide the “load resistor” on bothsides (patient side as well) so that there is symmetry in theimplementation and the protection device may be plugged in either way.

In some instances, with a protection device as implemented in FIG. 16 ,there may be introduction of switching artifacts and short voltagespikes on the patient. FIGS. 17A and 17B are schematic illustrations ofa time sequence of cardiac stimulation (1510), electrocardiogram (1520),pulsed field ablation delivery (1530), and protection interval (1540)channels, where a switching artifact (1526) may occur when a protectioninterval ends. FIG. 17A illustrates a single cardiac cycle and FIG. 17Billustrates a plurality of cardiac cycles, as described in more detailherein. The stimulation or pacing signal (1510) may be periodic and maycomprise a rectangular pulse having a width of between about 0.1 ms andabout 100 ms. In some embodiments, the pacing pulses (1512) may bedelivered using any of the pacing devices (e.g., pacing devices (230,630, 1030)) described herein. The pacing pulses (1512) may correspond toone or more of ventricular and atrial cardiac pacing. In response to thepacing pulses (1512), the cardiac cycle of the heart may synchronizewith the pacing pulses (1512). For example, the QRS waveform (1522) inFIGS. 17A and 17B is synchronized with the pacing pulse (1512).

In some embodiments, a pulse waveform (1532) and protection interval(1542) may synchronize with one or more of the pacing signal (1512) andthe cardiac cycle (e.g., via R-wave detection), as described inembodiments above. For example, a pulse waveform (1532) may have a firstlength and a protection interval (1542) may have a second length atleast as long as the first length. The pulse waveform (1532) may bedelivered after a first delay (1534) from a trailing edge (1514) of thecardiac pacing pulse (1512). The first delay (1534) may be apredetermined value. For example, the first delay (1534) may be betweenabout 1 ms and about 20 ms. Likewise, a protection interval (1542) maysynchronize with the cardiac pacing pulse (1512) after a second delay(1544). In this manner, a cardiac pacing signal (1512) may be configuredto trigger the pulse waveform (1532) and the protection interval (1542).

In embodiments including a protection device as implemented in FIG. 16 ,switching artifact (1526) (e.g., voltage spike) may be introduced in thepatient and picked up in the electrocardiogram (1520) (e.g., via anelectrocardiogram recording system) that may interfere with analysis ofcardiac activity. For example, a protection artifact (1526) may coincidewith a trailing edge (1528) of a protection interval (1542). FIG. 17Billustrates an embodiment where a protection interval (1542) is providedfor each heartbeat and may, for example, generate an artifact (1526) foreach protection interval/heartbeat. In some embodiments where lesscoordinated control of a protection device is available, one or moreprotection intervals (1542) may be provided without a correspondingpulse waveform (1532). This may occur, for example, in embodiments wherethe pulse waveform (1530) and protection signal (1540) are independentlysynchronized using different signals.

When artifacts (1526) are sufficiently large in magnitude, they cancause clinical misinterpretation of cardiac activity. To mitigate thisrisk, several options are available. First, the protection module can beintegrated with a signal generator such that the protection interval(1542) is provided only when there is a corresponding pulse waveform(1532) and not when a pulse waveform (1532) is not delivered.Accordingly, a protection interval (1542) is provided when necessary toelectrically isolate a cardiac stimulator or other protected electricalcomponents (e.g., monitoring equipment) from a high voltage pulsewaveform. With this implementation, no unnecessary protection-switchingoccurs, and for artifacts (1526) generated with a pulse waveform, thehigh voltage ablation energy delivered to heart tissue saturates theheartbeats such that the artifacts (1526) do not present an issue.

Second, for independent protection devices where less coordinatedcontrol with pulsed field ablation device is possible, switchingartifacts (1526) can be reduced, e.g., using placement of low-valuecapacitors across the isolation switches or between the protectedchannels to absorb some of the high-frequency local switching energy inthe protection device. The implementation of previously describedpassive filtering components, e.g., see FIG. 2 , can also be implementedto reduce artifacts (1526). Other options include using additionalswitches/MOSFETs to temporarily short pairs of signals together (e.g.,stimulator+/− and patient+/−) before re-connecting to the patient,temporarily switching in a resistive load on the patient-side during ablanking interval, etc.

FIG. 18 is a block diagram of electrical component(s) (1610) coupled toa patient (1620) via a protection device (1600) including one or morecapacitors for reducing artifacts. One or more electrical component(s)(1610) (e.g., monitoring equipment, cardiac stimulator) may be coupledto the patient (1620) via a protection device (1600) configured toselectively electrically isolate such components from devices disposedin the heart of the patient (1620). In some embodiments, the protectiondevice (1600) may be configured to reduce a magnitude of an artifact(e.g., artifact (1526)). The protection device (1600) can includecomponents that are structurally and/or functionally similar to any ofthe other protection devices described herein (e.g., protection devicesdepicted in FIGS. 3A, 3B, 4, 5, 8, 10A-10E, 11, 12, 14-16, and 19 ).

The protection device (1600) may include one or more series protectionswitches (1602) and resistors (1606). The protection device (1600) mayfurther include one or more of capacitors (1604) configured parallel tocorresponding switches (1602) and resistors (1606). The capacitors(1604) may be configured to receive a portion of any voltage spikegenerated by the switching operations of protection device (1600).Additionally or alternatively, the protection device (1600) may includeone or more circuit components described in FIG. 15 (e.g., filter device(1330), common mode protection device (1340), differential/high voltageprotection device (1350)) configured to reduce switching artifacts.

The resistors (1606) can be arranged in series with switches that can beconfigured to close prior to closing the series protection switches(1602) to reduce artifacts produced by the switching of the protectionswitches (1602). For example, the switches in series with the resistors(1606) may be configured to close prior to the series protectionswitches (1602) closing in order to provide a temporary pathways for oneor more of the electrical component(s) (1610) and the patient (1620),thereby reducing risk of artifacts from the series protection switches(1602) when the loads are subsequently disconnected.

FIG. 19 is a schematic diagram of a system for ablation via irreversibleelectroporation including a protection device (1900). The system mayinclude a signal generator (1930), ablation device (1932), andelectronic component(s) (1940). In some embodiments, the electroniccomponent(s) (1940) may be implemented as a signal detector, e.g., suchas monitoring equipment for monitoring physiological data of a patient(1920). The protection device (1900) can include component(s) that arestructurally and/or functionally similar to other protection devicesdescribed herein (e.g., protection devices depicted in FIGS. 3A, 3B, 4,5, 8, 10A-10E, 11, 12, 14-16, 18, and 19 ).

The signal generator (1930) may be configured to generate pulsewaveforms delivered to tissue by electrodes (not shown) of the ablationdevice (1932). In some embodiments, the signal generator (1930) may beconfigured to generate high voltage ablation pulse waveforms forirreversible electroporation of tissue, such as, for example, pulmonaryvein ostia. In some embodiments, the protection device (1900) may beelectrically coupled to the patient (1920) via a set of patientconnections (1924). For example, one or more electrode(s) and/orsensor(s) may be placed externally on and/or internally within thepatient (1920), e.g., to measure physiological data of the patient(1920). The protection device (1900) may be coupled between the patient(1920) and the electronic component(s) (1940).

In some embodiments, the signal generator (1922) may be configured togenerate the pulse waveform in synchronization with the indication of apacing signal and/or within a common refractory window. For example, insome embodiments, the common refractory window may start substantiallyimmediately following a pacing signal (or after a very small delay) andlast for a duration of approximately 250 milliseconds (ms) or lessthereafter. In such embodiments, an entire pulse waveform may bedelivered within this duration.

In some embodiments, the electronic components (1940), the protectiondevice (1900), and/or the signal generator (1930) may be incommunication with one another, e.g., for coordinating timing of thepulse waveform delivery and/or protection device control signaldelivery. For example, the signal generator (1930) can be operativelycoupled to the protection device (1900) such that the signal generator(1930) can deliver signals (e.g., a synchronization signal (1912)) tothe protection device (1900), e.g., for synchronizing operation of oneor more component(s) of the protection device (1900) with the deliveryof the ablation pulse waveform. In an embodiment, the signal generator(1930) can deliver a synchronization signal (1912) to the protectiondevice (1900) on a periodic basis that indicates to the protectiondevice (1900) of a delivery timing of the pulse waveform. As depicted inFIG. 19 , the signal generator (1930) and the protection device (1900)can be separate devices. Alternatively, in some embodiments, theprotection device (1900) may be integrated with the signal generator(1930) in a single console.

The protection device (1900) may be configured to form an open circuitbetween the electronic component(s) (1940) and one or more patientconnections (1924), e.g., sensor(s) or electrode(s) deposed near thesite of ablation, at least during delivery of ablation energy by theablation device (1932). The patient connections (1924) can allow theelectronic component(s) 1940 to monitor physiological data of thepatient (1920). As described herein, delivery of pulse waveforms to thepatient (1920) can induce high voltages and/or currents in patientconnections (1924). Accordingly, by isolating these connections (1924)from the electronic component(s) (1940), the protection device (1900)can reduce or prevent transfer of such induced voltages and/or currentsto the electronic component(s) (1940), thereby reducing noiseinterference from entering such components and/or damaging suchcomponents. When a pulse waveform is not being delivered to the patient(1920), the protection device (1900) may be configured to electricallycouple the electronic components (1940) with the patient connections(1924), e.g., to allow the electronic components (1940) to continue tomonitor physiological data of the patient (1920).

The protection device (1900) may comprise a set of one or more switches(e.g., series components) (1902) configured to form an open circuitbetween the patient connections (1924) and the electronic component(s)(1940). The set of switches (1902) can include one or more ofelectro-mechanical relays (e.g., reed relays), solid-state relays,and/or MOSFET devices.

In some embodiments, components can be introduced which can electricallyconnect the protected patient signals to a common node (1906). Theprotection device (1900), for example, can include channels that extendfrom each input into an electronic component (1940) and connect them toa common node (1906). Each channel can include a switch (1903) and aresistance element (1904) (e.g., a resistor). When the switches (1903)are closed, the channels can connect the inputs to the electroniccomponents (1940) to the common node (1906). The resistance elements(1904) may be coupled between the inputs and the common node (1906). Theresistance elements (1904) can be configured to reduce or minimizeresistance when connecting the inputs to the common node (1906). Duringpulsed field ablation (e.g., delivery of a pulse waveform), to reducenoise present at the input(s) of the electronic component(s) (1940)(e.g., monitoring equipment), the inputs can be shorted together toreduce the amplitude of any differential noise. The switches (1902) maybe open, e.g., to isolate the electronic component(s) (1940) from thepatient connection(s) (1924), but any residual noise that is transferredor picked up through the open-circuit series components (e.g., switches(1902)) during the pulsed field ablation delivery can be tied to thecommon node (1908) and the signal amplitude detected at the electroniccomponent(s) (1940) (e.g., measured by the monitoring equipment) can bereduced or rendered small.

In some embodiments, components can be introduced that can connect thecommon node (1906) to a ground (1909) (e.g., the chassis or earthground), e.g., to further reduce noise that can be picked up at theinput(s) to the electronic component(s) (1940) during pulsed fieldablation delivery. By coupling inputs that are electrically tiedtogether (e.g., via the common node (1906)) to a ground connection, theprotection device (1900) can reduce the amplitude of common mode noiseand prevent large DC voltages above earth ground from being transferredinto the electronic component(s) (1940) (e.g., an input amplifier of amonitoring device). Coupling the common node (1906) to ground (1909) canalso reduce the chances for interference from the pulsed field ablationdelivery affecting the electronic component(s) (1940).

In some embodiments, components can be introduced which can filterhigh-frequency signals on ground connections (e.g., earth-groundconnections) at the signal generator (1930) and/or the protection device(1900) (or other protection circuitry). For example, the signalgenerator (1930) may be coupled to ground via an inductance filter(e.g., a ferrite clamp, ferrite toroid, or series inductor) (1914).Additionally or alternatively, the protection device (1900) may becoupled to ground via inductance filter (e.g., ferrite) (1901). Thenoise created upon ablation delivery by the signal generator (1930) canbe conducted through the patient to the patient connection (1902), butit can also be emitted on the ground connection of the signal generator(1930). To reduce the noise caused by the connection of the signalgenerator (1930) to ground, components such as ferrite clamps, ferritetoroids, or series inductors (e.g., filter (1914)) may be used to filterthe high-frequency noise on these connections and to reduce theamplitude measured at the ground connection of the electroniccomponent(s) 1940.

FIGS. 20A-20C are schematic illustrations of time sequences ofestablishing connections among one or more of inputs or signals to theelectronic components (1940), the common node (1906), and ground (1909),during pulsed field ablation delivery. Time sequences (2012, 2014, 2016)represent timing of connecting the inputs to the electronic components(1940) to the common node (1906), time sequences (2022, 2024, 2026)represent timing of connecting the common node (1906) to the ground(1909), time sequences (2032, 2034, 2036) represent timing of formingthe open circuit between the patient connections (1924) and theelectronic component(s) (1940) using the series components or switches(1902), and time sequences (2042, 2044, 2046) represent the timing ofthe pulse waveform delivery (e.g., via the signal generator (1930)).

FIG. 20A illustrates a time sequence (2010) for operating the componentsof the protection device (1900) that ties the inputs to the electroniccomponents (1940) together via the common node (1906) and simultaneouslyties the common node (1906) to ground (1909), as shown by (2012, 2022).As depicted, the time sequence (2010) allows the electronic component(s)(1940) to continue to see a low-impedance load between its inputs (e.g.,from patient connections (1924)) throughout the ablation deliveryprocedure and ensures that the common mode DC level is low. The timesequence (2010) ensures that the inputs (e.g., from patient connections(1924)) to the electronic components are not high-impedance, which mayundesirably allow large noise pick-up. After the inputs to theelectronic components (1940) are tied together and to ground (1909), theseries components can form an open circuit (e.g., switches (1902) can beset to an open state) between the patient connections (1924) and theelectronic components (1940), which isolates the electronic components(1940) from the patient (1920), as shown by (2032). After the opencircuit is established, the pulse waveform can be delivered to ablatetissue, as shown by (2042). After the ablation procedure is complete andthe pulse waveform is no longer being delivered to the patient (1920),the series components can re-connect the patient (1920) to theelectronic equipment (1940). Then following that, the inputs to theelectronic components (1940) can be released from their common node andearth-ground connections (e.g., the switches (1903) can be set to anopen state), and the electronic components (1940) can again beconfigured to receive data (e.g., physiological data) from the patientconnections (1924), free of any pulsed field ablation interference.

FIG. 20B depicts another time sequence (2020) for operating thecomponents of the protection device (1900). The time sequence (2020) ofFIG. 20B is similar to the time sequence (2010) of FIG. 20A, except thatthe connection of the common node (1906) to ground (1909) does not occursimultaneously with the connection of the inputs of the electroniccomponents (1940) to the common node (1906). In some embodiments, theconnection of the common node (1906) to ground (1909) (e.g., switch(1908) switching to a closed state) may occur when the series componentsof the protection device (1900) transitions to the open circuitconfiguration (e.g., switches (1902) transition to the open state), asshown by (2024, 2034). This can ensure that the patient (1920) is nottemporarily earth-grounded (i.e., the patient connections (1924) are notcoupled to earth ground (1909)) after the inputs to the electroniccomponent(s) 1940 are connected to the common node (1906) but the seriescomponents have yet to transition into an open state. By not having thepatient (1920) temporarily earth-grounded, any residual current withinthe system does not have a pathway through the patient (1920) to ground.Then once the patient signals are open circuit (e.g., switches (1902)transition to the open state), energy (e.g., ablation pulse waveform)may be delivered to the patient (1920) and, upon completion of theenergy delivery, the patient signals can be re-connected (e.g., switches(1902) transition back to the closed state), simultaneous with therelease of the earth-ground connection (e.g., switch (1908) switchesback to an open state). Following these events, the inputs to theelectronic component(s) (1940) can be released from the common node(1906) to allow the electronic component(s) 1940 to measure patientsignals again via the patient connections (1924), without interferenceor noise from the ablation energy delivery.

FIG. 20C depicts another time sequence (2030) for operating thecomponents of the protection device (1900). The time sequence (2030) ofFIG. 20C is similar to the time sequences (2010, 2020) of FIGS. 20A and20B, except that a connection is not formed between the common node andthe ground at any point during the sequence, such that the common node(1906) is left floating. This may ensure that an earth ground (1909)input connection does not interfere with the inputs of the electroniccomponent(s) (1940). As described above, during an ablation procedure,high-frequency signals can travel from the signal generator (1030)and/or other components of the system to earth ground (1909). As such,establishing a connection with the ground (1909) can cause such signalsto interfere with the operation of the electronic components (1940),e.g., by generating noise. While the inductance filters (1901, 1914)described above can be used to reduce some of these high-frequencysignals, such inductance filters (1901, 1914) may need to be adjusted,based on whether various components of the system are in an open orclosed state, and therefore may be imperfect at filtering thehigh-frequency signals. Similar to the time sequences (2010, 2020), theseries components can be switched to an open circuit state and ablationenergy can be delivered while the series components are in the opencircuit state. Following delivery of the ablation energy, the seriescomponents can switch back to the closed circuit state, reconnecting thepatient connections (1924) to the electronic components (1940), and theinputs to the electronic component(s) 1940 can be released from thecommon node (1906) connection.

Methods

Also described here are methods for protecting electronic circuitry frominduced currents and voltages during a tissue ablation process performedin one or more heart chamber(s) using the systems and devices describedherein. In an embodiment, the heart chamber(s) may be the left atrialchamber and include its associated pulmonary veins. Generally, themethods described here include introducing and disposing a pacing device(e.g., pacing device (230)) in contact with one or more heartchamber(s). The pacing device may deliver a pacing signal to the heartusing a cardiac stimulator (e.g., cardiac stimulator (28, 28′)) and/ormeasure cardiac activity. An ablation device (e.g., ablation device(210)) may be introduced and disposed in contact with one or morepulmonary vein ostial or antral regions. A pulse waveform may bedelivered by one or more electrodes (e.g., electrodes (212)) of theablation device to ablate tissue. In some embodiments, a protectiondevice (e.g., protection device (250)) can be in an open-circuitconfiguration to isolate one or more sensitive electrical components(e.g., cardiac stimulator, monitoring equipment) during the delivery ofthe pulse waveform. Such electrical components may otherwise beelectrically coupled to the pacing device and configured to deliverpacing signals to the heart and/or receive cardiac activitymeasurements. In some embodiments, a control signal may be generated tocontrol the open-circuit interval (e.g., protection interval) of theprotection device. The control signal may be based on one or more of acardiac pacing signal, pulse waveform signal (e.g., signal generatorsignal), measured cardiac activity (e.g., R-wave detection),combinations thereof, and the like.

Additionally or alternatively, the pulse waveforms may include aplurality of levels of a hierarchy to reduce total energy delivery,e.g., as described in International Application Serial No.PCT/US2019/031135, filed on May 7, 2019, and titled “SYSTEMS,APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE,” andincorporated herein by reference.

In some embodiments, the ablation devices (e.g., ablation device (210))described herein may be used for epicardial and/or endocardial ablation.Examples of suitable ablation catheters are described in InternationalApplication Serial No. PCT/US2019/014226, incorporated by referenceabove.

FIG. 6A is an example method (400) of tissue ablation where ablationenergy is delivered in synchrony with cardiac pacing. In someembodiments, the voltage pulse waveforms described herein may be appliedduring a refractory period of the cardiac cycle so as to avoiddisruption of the sinus rhythm of the heart. The method (400) includesintroduction of a pacing device (e.g., pacing device (230)) into anendocardial space, e.g., of a right ventricle, at (402). The pacingdevice may be advanced to be disposed in contact with the cardiactissue, at (404). For example, sensor electrodes may be configured forcardiac activity measurement (e.g., ECG signals) and pacing electrodesmay be configured for delivering pacing signals and may be disposed incontact with an inner endocardial surface, for example in the rightventricle. An ablation device (e.g., ablation device (210)) may beintroduced into an endocardial space, e.g., of a left atrium, at (406).The ablation device may be advanced to be disposed in contact with apulmonary vein ostium, at (408). In some embodiments, a pacing signalmay be generated by a cardiac stimulator (e.g., cardiac stimulator (28,28′)) for cardiac stimulation of the heart, at (410). The pacing signalmay then be applied to the heart, at (412), using the pacing electrodesof the pacing device. For example, the heart may be electrically pacedwith the pacing signal to ensure pacing capture to establish periodicityand predictability of the cardiac cycle. One or more of atrial andventricular pacing may be applied. Examples of applied pacing signalsrelative to patient cardiac activity are described in more detailherein, e.g. FIG. 7B.

In some embodiments, pacing capture may be automatically confirmed byone or more of a signal generator (e.g., signal generator (222)), thecardiac stimulator, or other processor operatively coupled to one ormore components of the system. In some embodiments, pacing capture canbe confirmed by a user. For example, the user may confirm pacing captureusing a user interface (e.g., an input/output device such as a touchscreen monitor or other type of monitor) based on measured cardiacactivity signals. If the signal generator, processor, and/or the userviewing the displayed cardiac output, determines that there is anabsence of pacing capture, pulse waveform generation may be prohibitedand the user may be prompted to adjust system parameters by, forexample, repositioning the pacing device to improve tissue engagementand/or modify pacing signal parameters (e.g., pulse width, pulseamplitude, pulse frequency, etc.).

In some embodiments, the pacing device may measure cardiac activity(e.g., ECG signals) corresponding to electrical cardiac activity of theheart, at (414). For example, the measured cardiac activity may includea measured cardiac pacing pulse, R-wave, etc.

A control signal or protection signal may be generated based on one ormore of a cardiac pacing signal, pulse waveform signal (e.g., a signalreceived form a signal generator), measured cardiac activity (e.g.,R-wave detection, predetermined voltage thresholds), combinationsthereof, and the like, and applied to the protection device at (418).For example, the protection signal may be generated based on a cardiacpacing signal received from a cardiac stimulator (e.g., cardiacstimulator (28)) or a ECG signal measured by the pacing device (e.g.,pacing device (230)). As another example, the protection signal may begenerated based at least in part on a pulse waveform signal receivedfrom a signal generator (e.g., signal generator (222)). The protectionsignal may have a predetermined time period and length. The cardiacstimulator and/or other electronic components may be electricallyisolated throughout a protection interval in response to the protectionsignal, at (418). For example, a protection device coupled to a pacingdevice may electrically isolate the cardiac stimulator from high voltagepulsed electric field ablation signals delivered by an ablation system(e.g., signal generator (222), ablation device (210), etc.) based on areceived protection signal.

In some embodiments, a protection signal may synchronize electricalisolation of a cardiac stimulator with delivery of ablation energy totissue. For example, the protection signal may be generated based on oneor more of a cardiac pacing signal, measured cardiac activity, andsignal generator signal, as described in detail herein. Additionally oralternatively, a protection device may generate a protection signal evenwhen a cardiac stimulator is not actively delivering pacing signalsduring a pulsed electric field ablation procedure. This may be useful,for example, in case of a medical emergency requiring rapid cardiacpacing. Such protection can also be useful to isolate electroniccomponents (e.g., medical electronic equipment other than the ablationdevice including, without limitation, ECG recording or monitoringequipment, electroanatomical mapping systems, device navigation/trackingsystems, etc.) that are often present in a clinical procedure room. Itis important to note that subsequent to delivery of a set of ablationpulses, the protection device is deactivated (424) so that connectionsare restored between the medical device electrode(s) and the respectiveelectronic component(s) (e.g., medical electronic equipment, cardiacstimulator, electroanatomical mapping system, ECG recording ormonitoring system, device navigation/tracking system, etc.).

The signal generator (e.g., signal generator (222) or any processorassociated therewith may be configured to generate a pulse waveform insynchronization with the protection interval, at (420), e.g., based onpredetermined criteria. For example, the pulse waveform may be generatedduring a refractory time period, which starts after and ends before theprotection interval. The refractory time period may follow a pacingsignal. For example, a common refractory time period may be between bothatrial and ventricular refractory time windows. A voltage pulse waveformmay be applied in the common refractory time period. In someembodiments, the pulse waveform and/or protection signal may begenerated with a time offset with respect to the indication of thepacing signal. For example, the start of a refractory time period may beoffset from the pacing signal by a time offset. The voltage pulsewaveform(s) may be applied over a series of heartbeats overcorresponding common refractory time periods. In some embodiments, thepulse waveform and protection signal may be generated based on the sameor different signal or information (e.g., pacing signal, sensed R-wave).

The ablation device, in response to receiving the pulse waveform, cangenerate an electric field (e.g., pulsed electric field) that isdelivered to tissue, at (422).

In some embodiments, hierarchical voltage pulse waveforms having anested structure and a hierarchy of time intervals as described hereinmay be useful for irreversible electroporation, providing control andselectivity in different tissue types. For example, a pulse waveform maybe generated by a signal generator (e.g., the signal generator (222))and may include a plurality of levels in a hierarchy. A variety ofhierarchical waveforms may be generated with a signal generator asdisclosed herein. For example, the pulse waveform may include a firstlevel of a hierarchy of the pulse waveform including a first set ofpulses. Each pulse has a pulse time duration and a first time intervalseparating successive pulses. A second level of the hierarchy of thepulse waveform may include a plurality of first sets of pulses as asecond set of pulses. A second time interval may separate successivefirst sets of pulses. The second time interval may be at least threetimes the duration of the first time interval. A third level of thehierarchy of the pulse waveform may include a plurality of second setsof pulses as a third set of pulses. A third time interval may separatesuccessive second sets of pulses. The third time interval may be atleast thirty times the duration of the second level time interval.

In some embodiments, the pulse waveform may be delivered to pulmonaryvein ostium of a patient via a set of splines of an ablation device(e.g., ablation device (210)), or to a device positioned at any locationin the cardiac anatomy or more generally in other parts of the patientanatomy. In some embodiments, voltage pulse waveforms as describedherein may be selectively delivered to electrode subsets such asanode-cathode subsets for ablation and isolation of the pulmonary vein.For example, a first electrode of a group of electrodes may beconfigured as an anode and a second electrode of the group of electrodesmay be configured as a cathode. These steps may be repeated for adesired number of pulmonary vein ostial or antral regions to have beenablated (e.g., 1, 2, 3, or 4 ostia). Suitable examples of ablationdevices and methods are described in International Application No.PCT/US2019/014226, incorporated above by reference.

FIG. 6B is an example method (1900) of tissue ablation where ablationenergy is delivered asynchronously (with no cardiac pacing). Theablation device is introduced in the patient anatomy and positioned in aregion of interest, for example at a location in the cardiac anatomywhere it is desired to ablate, at (1905). The protection device may beactivated at (1909), e.g., by a suitable control signal that may becoupled directly to hardware switched isolation circuitry or to aprocessor that controls switched isolation circuitry. As used herein, acontrol element may refer to one or more of a control signal, processor,and a switch circuit (e.g., switched isolation circuitry). Thus, theelectronic components or equipment to be protected are isolated frompossible pickup of ablation pulses over an isolation time interval. Apulse waveform is generated at (1913) and delivered to tissue at (1917)within the isolation time interval. Subsequent to delivery of theablation pulses at (1917), the protection device is deactivated at(1920) so as to restore electrical connectivity between the electroniccomponent(s) or equipment and any relevant patient-contact electrodes.Such protected electronic equipment can include one or more cardiacstimulators, electroanatomical mapping systems, ECG recording/monitoringsystems, device navigation/tracking systems, etc.

For example, in embodiments where a cardiac stimulator is used to pace aheart over portions of a pulsed electric field ablation procedure, apatient connection between the cardiac stimulator and the heart needs toremain intact for the duration of a pacing or stimulation pulse. In suchembodiments, a protection signal (e.g., control signal for activating aprotection device) can synchronize electrical isolation of a cardiacstimulator with delivery of ablation energy to tissue. FIG. 7A is aschematic illustration of a time sequence of cardiac stimulation (510),pulsed electric field ablation delivery (530), and protection interval(540) (e.g., blanking or open-circuit) channels. FIG. 7B is a schematicillustration of a time sequence of cardiac stimulation (510),electrocardiogram (520), pulsed electric field ablation delivery (530),and protection interval (540) channels. The cardiac stimulation (510)may comprise a set of periodic pacing pulses (512). Each pacing pulse(512) may comprise a rectangular pulse having a width of between about0.1 ms and about 20 ms. The pacing pulses (512) may be generated by astimulator (e.g., stimulator (28, 28′)) and delivered to cardiac tissueusing a pacing device (e.g., pacing device (230)). The pacing pulses(512) may correspond to one or more of ventricular and atrial cardiacpacing. In response to the pacing pulses (512), the cardiac cycle of theheart may synchronize with the pacing pulses (512). For example, the QRSwaveform (522) in FIG. 7B is synchronized with a respective pacing pulse(512). The T-wave (524) that follows the QRS waveform (522) correspondsto the start of repolarization occurring in the cardiac myocytes. Insome embodiments, electrocardiogram (520) may be measured using a pacingdevice.

In some embodiments, high-voltage application of a pulsed electric fieldablation procedure can be synchronized with the cardiac cycle, asdepicted in FIGS. 7A and 7B. Pacing can be synchronized to thehigh-voltage application in several ways. For example, atrial pacing,ventricular pacing, or multi-chamber pacing can be performed. It can bedesirable to implement ventricular pacing as the ventricle is more proneto cause arrhythmias (e.g., ventricular tachycardia, ventricularfibrillation) if stimulated during its re-polarization (e.g., T-wave)period. When a stimulation pulse is applied, the high-voltage output ofthe pulsed electric field ablation can occur concurrent with the pacingor being a predetermined delay after the stimulation pulse.

In some embodiments, delivery of a pulse waveform (532) may begin afirst delay (534) (e.g., time interval or period) after the trailingedge (514) of each pacing pulse (512). Each pulse waveform (532) can beapplied during an interval (532). In some embodiments, the first delay(534) may be a predetermined value (e.g., input by a user). For example,the first delay (534) may be between about 1 ms and about 100 ms. Asecond pulse delay (536) can separate the end of the pulse waveform(532) delivery and the start of the T-wave. As described above, it canbe desirable to deliver a pulse waveform during a refractory periodassociated with a cardiac cycle. Accordingly, this second pulse delay(536) represents a safety margin between the pulse waveform (532) andthe T-wave (524).

A blanking interval or protection interval (542) can be configured tostart immediately or shortly after each pacing pulse (512). Theprotection interval (542) can be configured to encapsulate the durationduring which the pulse waveform (532) is delivered. For example, theprotection interval (542) can begin a third delay (544) after thetrailing edge (514) of the pacing pulse (512), where the third delay(544) is less than the first delay (534) of the pulse waveform (532).For example, the third delay (544) may be less than about 5 ms. Thethird delay (544) can be near zero but non-zero such that the protectioninterval (542) (e.g., open-circuit state, blanking interval) does notoverlap the pacing pulse (512) since a closed-circuit connection isnecessary for a stimulator and pacing device to deliver the pacing pulse(512). In some embodiments, the protection interval (542) is at leastequal to and preferably greater than a first length of the pulsewaveform (532) such that the protection interval (542) at least overlaps(e.g., encapsulates) the entire pulse waveform (532). In FIGS. 7A and7B, the leading and trailing edges (550) of the pulse waveform (532) andprotection interval (542) are such that the protection interval (542) islonger than the pulse waveform (532).

If the timing of the high-voltage application of the pulsed electricfield ablation is known (e.g., with respect to the pacing or stimulationpulses of the cardiac stimulator), the protection interval (542) can betailored around the duration of the high-voltage application to ensurethat isolation protection encapsulates the high-voltage applicationinterval. The signal generator for the high-voltage application can beconfigured to have a predetermined amount of delay (e.g., first delay(534)) between the stimulation pulse (e.g., pacing pulse (512)) and theinitiation of the high-voltage application to the patient (e.g., leadingedge (550) of pulse waveform (532)). This delay can provide sufficienttime for the protection element to transition to its isolation state(e.g., open circuit state or configuration) and start the protectioninterval (542). The protection interval (542) then remains for aduration longer than the high-voltage application interval. The timingof the protection interval (542) and the pulse waveform (532) can berepeated for each cardiac cycle.

In some embodiments, cardiac sensing or monitoring e.g., for an R-wave(e.g., ventricular depolarization/contraction) can be used tosynchronize delivery of ablation energy to tissue to the cardiac cycle.For example, the intrinsic R-wave of patient can be sensed and used as atrigger to one or more of ablation energy delivery and electricalisolation. In some embodiments, this R-wave sensing can be used in lieuof pacing the heart. In alternative embodiments, the R-wave sensing canbe used along with pacing. For example, pacing can be performed ineither the atria or ventricles, and the R-wave response of the capturedbeat can be sensed and used for synchronization. FIG. 8 is a schematicdiagram of an electroporation system disposed in a heart (602) of apatient (600). The electroporation system may include an ablation device(610), signal generator (622) (e.g., pulsed field ablation generator),cardiac stimulator (628), pacing device (630), protection device (650),and one or more signal detectors (670, 672). While two signal detectors(670, 672) are depicted in FIG. 8 , it can be appreciated that a singlesignal detector rather than two independent detectors can be used toaccomplish the methods described herein.

The signal generator (622) may be coupled to the ablation device (610)and the signal detector (672). The signal generator (622) may beconfigured to generate pulse waveforms delivered to electrodes (612) ofthe ablation device (610), e.g., for delivering ablation energy to theheart (602). The pacing device (630) may be configured to pace the heartusing pacing electrodes (632) of pacing device (630). One or morediagnostic devices (636) may be configured to measure cardiac activityof the heart (600) (e.g., electrocardiogram), e.g., using externallyplaced electrode pads or intra-cardiac electrodes (634). Alternatively,in some embodiments, one or more electrodes of the pacing device (630)and/or ablation device (610) can be used as sensing electrodes, whichcan connect to a processor (e.g., signal detector (670, 672)) forfurther detection and/or analysis of components of the cardiac cycle.

The protection device (650) may be coupled between the cardiacstimulator (628) and the pacing device (630). In some embodiments, theprotection device (650) may be configured to synchronize electricalisolation of the cardiac stimulator (628) with delivery of ablationenergy by the ablation device (610). The one or more signal detectors(670, 672) may be coupled to one or more of the signal generator (622),pacing device (630), protection device (650), and cardiac stimulator(628). As shown in FIG. 8 , a first signal detector (670) is coupled tothe protection device (650) and a second signal detector (672) iscoupled to the signal generator (622). In alternative embodiments,however, a single signal detector can be coupled to both the protectiondevice (650) and the signal generator (622).

Each signal detector (670, 672) may be coupled to a respectivediagnostic device (636) coupled to the patient (600). Alternatively, thesignal detectors (670, 672) may be integrated with one or more of thesignal generator (622), pacing device (630), protection device (650),and cardiac stimulator (628). The signal analyzer (670) may beconfigured to receive and analyze an electrocardiogram signal to detectone or more R-waves. In some embodiments, R-waves may be detected usingan R-wave amplitude threshold, together with some exclusion criteria fornoise. When an R-wave is detected, the signal detector (670, 672) can beconfigured to output a signal to the protection device (650) and signalgenerator (622). Specifically, the signal detector (672) coupled to thesignal generator (622), upon detecting an R-wave, can send a signal tothe signal generator (622) to indicate the timing of the R-wave andtherefore inform the signal generator (622) as to when to deliver thepulsed electric field ablation. The signal detector (670) coupled to theprotection device (650), upon detecting an R-wave, can send a signal tothe protection device (650) (e.g., a control signal as described above)to indicate the timing of the R-wave and therefore inform protectiondevice (650) of when to initiate the protection or blanking interval, asfurther described with reference to FIG. 9 .

FIG. 9 is a schematic illustration of a time sequence of cardiacstimulation (710), electrocardiogram (720), pulsed field ablationdelivery (730), and protection interval (740) channels. The timesequence depicted in FIG. 9 can include aspects similar to the timesequence depicted in FIG. 7B. The cardiac stimulation (710), e.g., by acardiac stimulator (628) as depicted in FIG. 8 , can provide optionaland/or periodic stimulation pulses (712) to a patient (e.g., patient(600)). In an embodiment, the stimulation pulses may be periodic and maycomprise a rectangular pulse having a width of between about 1 ms andabout 5 ms. In some embodiments, the pacing pulses (712) may bedelivered using any of the pacing devices (e.g., pacing device (630))described herein. The pacing pulses (712) may correspond to one or moreof ventricular and atrial cardiac pacing. The electrocardiogram (720)can include one or more P-waves (721), QRS waveforms (722), and T-waves(724). The P-wave (721) corresponds to atrial depolarization. The T-wave(724) that follows the QRS waveform (722) corresponds to the start ofrepolarization occurring in the cardiac myocytes. In some embodiments,delivery of a pulse waveform (732) may be synchronized with R-wave (726)detection, e.g., immediately upon R-wave detection or after a firstdelay (734). In embodiments where a protection device (e.g., protectiondevice (650)) is used to isolate certain electronic components from thepatient during pulsed electric field ablation delivery, it can bedesirable to implement a predetermined delay such that there issufficient time for the protection device to isolate such electroniccomponents after R-wave detection and before pulsed electric fieldablation delivery. In some embodiments, the first delay (734) may be apredetermined value. For example, the first delay (734) may be betweenabout 1 ms and about 5 ms. In some embodiments, the pulse waveform (732)may be separated from a T-wave (724) by a second delay (736), e.g., toprovide a safety margin.

In some embodiments, a protection device (e.g., protection device (650))that implements a protection interval (742) (e.g., open-circuit orblanking interval) can use R-wave (726) detection for synchronization.The protection device can start the protection interval (742) after athird delay (744) from the R-wave (726). The third delay (744) may beless than the first delay (734). The third delay (744) may be less thanabout 5 ms. When a protection device is used with cardiac stimulation,the protection interval (742) (e.g., open-circuit state, blankinginterval) can be configured to not overlap the stimulation or pacingpulse (712). The protection interval (742) may be at least equal to, andpreferably greater than, a length of the pulse waveform (732) such thatthe protection interval (742) at least overlaps (e.g., encapsulates) theentire pulse waveform (732). In some embodiments, the pulse waveform(732) and the protection interval (742) can be implemented independently(e.g., with separate R-wave detectors (670, 672)) or concurrently (e.g.,with a single R-wave detector (670)). By starting the protectioninterval (742) immediately or shortly after R-wave (726) detection andhaving it continue for longer than the expected pulsed field ablationdelivery duration, the protection interval (742) can protect electroniccomponents (e.g., sensitive equipment such as, for example, the cardiacstimulator) even when intra-cardiac pacing is not actively being usedduring a pulsed field ablation procedure. It can be important to protectsuch electronic components such as a cardiac stimulator, even if suchequipment is not actively being used during an ablation procedure, inthe event of medical emergencies that may require rapid pacing or othertypes of pacing and therefore permitting such electronic components tobe functional, connected, and ready to use throughout the procedure.

Protection or isolation coverage of certain electronic components duringa high voltage interval can be implemented using a fixed blankinginterval sufficiently long in duration to cover a longest expectedablation interval or an adjustable or settable blanking interval (e.g.,which a user or system can set to a value based on expected pulsed fieldablation time). FIG. 13 is a schematic illustration of a time sequenceof a cardiac stimulation (1110), electrocardiogram (1120), pulsed fieldablation delivery (1130), and protection interval (1140) channels. Thecardiac stimulation (1110) channel can optionally include pacing orstimulation signals (1112) that may be periodic and may comprise arectangular pulse having a width of between about 0.1 ms and about 100ms. In some embodiments, the pacing pulses (1112) may be delivered usingany of the pacing devices (e.g., pacing devices (230, 630, 1030))described herein. The pacing pulses (1112) may correspond to one or moreof ventricular and atrial cardiac pacing. In response to the pacingpulses (1112), the cardiac cycle of the heart may synchronize with thepacing pulses (1112). For example, the P-wave (1121), QRS waveform(1122), and T-wave (1124) in FIG. 13 can be synchronized with the pacingpulse (1112). The P-wave (1121) corresponds to atrial depolarization,and the T-wave (1124) that follows the QRS waveform (1122) correspondsto the start of repolarization occurring in the cardiac myocytes.

In some embodiments, a pulse waveform (1132) and protection interval(1142) may synchronize based on one or more of pacing or stimulationpulse sensing (1144) and R-wave detection (1124). The pulse waveform(1132) may have a first length or duration (1134), and the protectioninterval (1142) may have a second length or duration (1148) at least aslong as the duration of the pulse waveform (1132). The duration (1148)of the protection interval (1142) can be fixed or adjustable. The pulsewaveform (1134) may be delivered after a first delay (1136) from atrailing edge (1114) of the cardiac pacing pulse (1112) (e.g., assignaled by a cardiac stimulator or detected). The first delay (1136)may be a predetermined value. For example, the first delay (1136) may bebetween about 1 ms and about 5 ms. Likewise, a protection interval(1142) may synchronize with the cardiac pacing pulse (1112) (e.g., assignaled by a cardiac stimulator or detected) after a second delay(1144). In this manner, a cardiac pacing signal (1112) may be configuredto trigger the protection interval (1142). The protection interval(1142) (e.g., open-circuit state, blanking interval) can overlap theentire pulse waveform (1132).

In some embodiments, the pulse waveform (1132) and protection interval(1142) may synchronize with R-wave detection (1124), e.g., afterrespective third delay (1138) and fourth delay (1146). In this manner,the R-wave detection (1124) may be configured to trigger the protectioninterval (1142). The R-wave detection can be implemented using any ofthe systems as described herein. The third delay (1138) may be apredetermined value. For example, the third delay (1138) may be betweenabout 1 ms and about 20 ms. In some embodiments, the pulse waveform(1132) and the protection interval (1142) may begin substantiallyconcurrently with the R-wave detection (1124).

In some embodiments, one or both of the second delay (1144) and thefourth delay (1146) can be adjustable such that the protection interval(1142) can have a duration (1148) that is adjustable.

It should be understood that the examples and illustrations in thisdisclosure serve exemplary purposes and departures and variations suchnumber of electrodes, sensors, and devices, and so on can be built anddeployed according to the teachings herein without departing from thescope of this invention. In particular, whether ablation energy withhigh voltage pulse waveforms is delivered synchronously with cardiacpacing or asynchronously (e.g., without cardiac pacing), the systems,devices, and methods disclosed herein can be configured to protect awide variety of medical electronic equipment including but not limitedto cardiac stimulators, electroanatomical mapping systems, ECG recordingsystems, ECG monitoring systems, device navigation or tracking systems,etc. It should be appreciated that the protection device embodimentsdescribed herein can be implemented in multi-channel formats that canprotect multiple device electrodes or sets of device electrodes that maybe connected to such electronic equipment. For example, the protectiondevice can incorporate 2, 4, 6, 8, 64, 256, or 512 channels ofprotection. Furthermore, the control signal used for activation of theprotection device(s) can be output to multiple such devices, thusproviding an expandable protection device where the number of channelsof protection can be expanded in modular fashion.

As used herein, the terms “about” and/or “approximately” when used inconjunction with numerical values and/or ranges generally refer to thosenumerical values and/or ranges near to a recited numerical value and/orrange. In some instances, the terms “about” and “approximately” may meanwithin ±10% of the recited value. For example, in some instances, “about100 [units]” may mean within ±10% of 100 (e.g., from 90 to 110). Theterms “about” and “approximately” may be used interchangeably.

Some embodiments described herein relate to a computer storage productwith a non-transitory computer-readable medium (also may be referred toas a non-transitory processor-readable medium) having instructions orcomputer code thereon for performing various computer-implementedoperations. The computer-readable medium (or processor-readable medium)is non-transitory in the sense that it does not include transitorypropagating signals per se (e.g., a propagating electromagnetic wavecarrying information on a transmission medium such as space or a cable).The media and computer code (also may be referred to as code oralgorithm) may be those designed and constructed for the specificpurpose or purposes. Examples of non-transitory computer-readable mediainclude, but are not limited to, magnetic storage media such as harddisks, floppy disks, and magnetic tape; optical storage media such asCompact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read OnlyMemories (CD-ROMs), and holographic devices; magneto-optical storagemedia such as optical disks; carrier wave signal processing modules; andhardware devices that are specially configured to store and executeprogram code, such as Application-Specific Integrated Circuits (ASICs),Programmable Logic Devices (PLDs), Read-Only Memory (ROM) andRandom-Access Memory (RAM) devices. Other embodiments described hereinrelate to a computer program product, which may include, for example,the instructions and/or computer code disclosed herein.

The systems, devices, and/or methods described herein may be performedby software (executed on hardware), hardware, or a combination thereof.Hardware modules may include, for example, a general-purpose processor(or microprocessor or microcontroller), a field programmable gate array(FPGA), and/or an application specific integrated circuit (A SIC)Software modules (executed on hardware) may be expressed in a variety ofsoftware languages (e.g., computer code), including C, C++, Java®, Ruby,Visual Basic®, and/or other object-oriented, procedural, or otherprogramming language and development tools. Examples of computer codeinclude, but are not limited to, micro-code or micro-instructions,machine instructions, such as produced by a compiler, code used toproduce a web service, and files containing higher-level instructionsthat are executed by a computer using an interpreter. Additionalexamples of computer code include, but are not limited to, controlsignals, encrypted code, and compressed code.

The specific examples and descriptions herein are exemplary in natureand embodiments may be developed by those skilled in the art based onthe material taught herein without departing from the scope of thepresent invention.

We claim:
 1. A system, comprising: a set of ablation electrodesdisposable near cardiac tissue of a heart; one or more sensorsdisposable near patient anatomy spaced from the set of electrodes, theset of sensors configured to be selectively coupled to and decoupledfrom an electronic device; a signal generator configured to generate apulse waveform, the signal generator coupled to the set of electrodesand configured to repeatedly deliver the pulse waveform to the set ofelectrodes; a protection circuit configured to selectively couple anddecouple the electronic device to and from the set of the sensors, theprotection circuit including a plurality of sets of switches, including:a first set of switches configured to switch between a conducting statein which the electronic device is coupled to the set of sensors, and anon-conducting state in which the electronic device is decoupled fromthe set of sensors; and a second set of switches configured toselectively couple and decouple a set of channels associated with theset of sensors to and from a common node; and a processor coupled to theprotection circuit, the processor configured to: control the first setof switches to cause the first set of switches to transition from theconducting state to the non-conducting state during a first timeinterval; and control the second set of switches to couple the set ofchannels to the common node during a second time interval, wherein thesecond time interval begins before and ends after the first timeinterval.
 2. The system of claim 1, wherein the first time intervalbegins before and ends after each delivery of the pulse waveform to theset of electrodes.
 3. The system of claim 2, further comprising theelectronic device, the electronic device including at least one of: anelectroanatomical mapping system configured to generate a map of cardiacelectrical activity; a device tracking and navigation system configuredto generate an anatomical map of a cardiac chamber; or anelectrocardiogram (ECG) system configured to monitor cardiac electricalactivity.
 4. The system of claim 1, further comprising a signal detectorconfigured to detect an R-wave associated with each cardiac cycle from aset of cardiac cycles, the signal generator configured to deliver thepulse waveform during each cardiac cycle from the set of cardiac cyclesafter detection of the R-wave of that cardiac cycle.
 5. The system ofclaim 4, wherein the signal generator is configured to deliver the pulsewaveform spaced from the R-wave of each cardiac cycle from the set ofcardiac cycles by a time delay, the time delay enabling the electronicdevice to be decoupled from the set of sensors before delivery of thepulse waveform.
 6. The system of claim 5, wherein the processor isfurther configured to: receive trigger signals from the signal detector,each trigger signal indicating when the R-wave has been detected,wherein the processor is configured to control the first set of switchesto switch to the non-conducting state in response to receiving eachtrigger signal; and the processor is further configured to transitionthe first set of switches into the conducting state after each deliveryof the pulse waveform.
 7. The system of claim 1, wherein the first setof switches includes one or more relay switches or metal-oxidesemiconductor field-effect transistor (MOSFET) switches.
 8. The systemof claim 6, wherein the protection circuit further includes one or moreof: a common mode choke, a differential mode choke, or a filter circuit.9. The system of claim 1, wherein the protection circuit furtherincludes at least (i) one or more capacitors, or (ii) switched-inresistors configured to absorb energy associated with the first set ofswitches transitioning between the conducting state and thenon-conducting state.
 10. The system of claim 9, wherein the protectioncircuit further includes a third switch configured to selectively coupleand decouple the common node to an earth ground, and wherein theprocessor is further configured to control the third switch to couplethe common node to the earth ground during a third interval of timebeginning before and ending after each delivery of the pulse waveform tothe set of electrodes.
 11. The system of claim 10, wherein the thirdinterval is equal to at least one of the first interval or the secondinterval.
 12. A method of controlling a pulsed field ablation system,the pulsed field ablation system comprising a signal generatorconfigured to generate a pulse waveform, a set of electrodes configuredto receive the pulse waveform and generate a pulsed electric field inresponse to the received pulsed waveform, a set of sensors disposed nearthe set of electrodes and capable of being selectively coupled anddecoupled to and from an electronic device, a processor, and aprotection circuit, the method comprising: prior to delivering the pulsewaveform to the set of electrodes: coupling, via the protection circuit,a set of channels associated with the set of sensors to a common node;decoupling, via the protection circuit, the set of sensors from theelectronic device after coupling the set of channels to the common node;delivering the pulse waveform to the set of electrodes disposed nearcardiac tissue; after delivering of the pulse waveform to the set ofelectrodes: coupling, via the protection circuit, the set of sensors tothe electronic device; and decoupling, via the protection circuit, theset of channels from the common node.
 13. The method of claim 12,further comprising, after coupling the set of channels to the commonnode and prior to delivering the pulse waveform to the set ofelectrodes, coupling the common node to an earth ground.
 14. The methodof claim 12, further comprising detecting an R-wave associated with eachcardiac cycle from a set of cardiac cycles, wherein delivering the pulsewaveform to the set of electrodes includes delivering the pulse waveformduring each cardiac cycle from the set of cardiac cycles after detectionof the R-wave of that cardiac cycle.
 15. The method of claim 14, furthercomprising receiving, by the processor, trigger signals from a signaldetector, each trigger signal indicating when the R-wave has beendetected.
 16. A system, comprising: an ablation device including a setof electrodes disposable near cardiac tissue of a heart; a signalgenerator configured to generate a pulse waveform, the signal generatorcoupled to the set of electrodes and configured to repeatedly deliverthe pulse waveform to the set of electrodes, the set of electrodes, inresponse to each delivery of the pulse waveform, configured to generatea pulsed electric field to ablate the cardiac tissue and to inducevoltages and currents in a set of sensors disposed near the ablationdevice; a protection circuit configured to selectively couple anddecouple an electronic device to and from the set of the sensors whilethe signal generator remains coupled to the set of electrodes, theprotection circuit configured to transition between a closed-circuitconfiguration in which the set of sensors are coupled to the electronicdevice and an open-circuit configuration in which the set of sensors aredecoupled from the electronic device, the protection circuit comprisinga first set of switches and a second set of switches; and a processorcoupled to the protection circuit, the processor configured to controlthe protection circuit to: during a first time interval, cause the firstset of switches to transition from a conducting state in which the setof sensors is coupled to the electronic device to a non-conducting statein which the set of sensors is decoupled from the electronic device; andduring a second time interval that begins before and ends after thefirst time interval, cause the second set of switches to couple a set ofchannels associated with the set of sensors to a common node, whereinthe first and second time intervals begin before and end after eachdelivery of the pulse waveform to the set of electrodes.
 17. The systemof claim 16, wherein each of the first and second set of switchesincludes one or more relay switches or metal-oxide semiconductorfield-effect transistor (MOSFET) switches.
 18. The system of claim 16,wherein the set of switches is a first set of switches, the protectioncircuit further including a third set of switches configured to be in aconducting state when the protection circuit is powered off and anon-conducting state when the protection circuit is powered on, each ofthe third set of switches being arranged in parallel to one of the firstset of switches such that the electronic device is coupled to the set ofsensors when the protection circuit is powered off.
 19. The system ofclaim 16, wherein the protection circuit further includes one or moreof: a common mode choke, a differential mode choke, or a filter circuit.20. The system of claim 16, wherein the protection circuit furtherincludes at least (i) one or more capacitors, or (ii) switched-inresistors configured to absorb energy associated with the set ofswitches switching between the conducting state and the non-conductingstate.